Zalata Khaled R, Nasif Wesam A, Ming Si-Chun, Lotfy Mahmoud, Nada Nadia A, El-Hak Nabil Gad, Leech Stephen H
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Cell Oncol. 2005;27(4):245-53. doi: 10.1155/2005/547010.
Oncogenes and tumor suppressor genes expression are well described in bladder cancer associated with schistosomiasis especially in Egypt. Scarce studies were directed to colorectal cancer (CRC) associated with Schistosoma mansoni (S. mansoni). Apoptosis (programmed cell death) and the genes regulating this process (e.g., Bcl-2) have recently become a focus of interest in the study of cancer development and progression. In the present study, we aimed to investigate the expression pattern of p53, Bcl-2 and C-Myc in CRC tissues obtained from Egyptian colorectal cancer patients divided in two different groups, one associated with Schistosoma mansoni (CRC-Sm) and the other without Schistosoma mansoni (CRC-NSm).
Seventy-five CRC tumors containing 36 draining lymph node metastatic tumors were immunohistochemically stained using specific monoclonal antibodies for p53, Bcl-2 and C-Myc, in addition the apoptotic activity of these tumors were analyzed.
Regardless of the S. mansoni infection, the obtained results showed that the apoptotic activity was more evident in p53 diffuse positive tumors (P = 0.021). There was a significant correlation between p53 diffuse positive staining and Bcl-2 positive immunostaining (P = 0.011). Signet ring cell carcinoma and mucinous adenocarcinoma exhibited both intense C-Myc expression than non-mucinous carcinoma (P = 0.001). When adjusting for S. mansoni infection, 58.3% of CRC-Sm cases were Bcl-2 positive compared to only (33.3%) of CRC-NSm (P = 0.046). Apoptotic activity was more evident in the latter group than of CRC-Sm tumors (P = 0.009). p53 and C-Myc expressions were found insignificantly different in CRC-Sm compared with CRC-NSm (P > 0.05). These observations suggest that the genotoxic agents produced endogenously through the course of schistosomiasis mansoni may play a role in CRC-Sm pathogenesis through the dysregulation of apoptosis by alteration the expression pattern of Bcl-2 protein differently from CRC-NSm suggesting a different biological behavior.
致癌基因和抑癌基因的表达在与血吸虫病相关的膀胱癌中已有充分描述,尤其是在埃及。针对与曼氏血吸虫相关的结直肠癌(CRC)的研究较少。凋亡(程序性细胞死亡)以及调节这一过程的基因(如Bcl-2)最近已成为癌症发生和发展研究的关注焦点。在本研究中,我们旨在调查从埃及结直肠癌患者获得的CRC组织中p53、Bcl-2和C-Myc的表达模式,这些患者分为两个不同组,一组与曼氏血吸虫相关(CRC-Sm),另一组无曼氏血吸虫(CRC-NSm)。
使用针对p53、Bcl-2和C-Myc的特异性单克隆抗体对75个CRC肿瘤(包括36个引流淋巴结转移瘤)进行免疫组织化学染色,此外还分析了这些肿瘤的凋亡活性。
无论是否感染曼氏血吸虫,所得结果表明凋亡活性在p53弥漫阳性肿瘤中更明显(P = 0.021)。p53弥漫阳性染色与Bcl-2阳性免疫染色之间存在显著相关性(P = 0.011)。印戒细胞癌和黏液腺癌的C-Myc表达均比非黏液癌强烈(P = 0.001)。在调整曼氏血吸虫感染因素后,58.3%的CRC-Sm病例Bcl-2呈阳性,而CRC-NSm组仅为(33.3%)(P = 0.046)。凋亡活性在后者组中比CRC-Sm肿瘤更明显(P = 0.009)。与CRC-NSm相比,CRC-Sm中p53和C-Myc的表达无显著差异(P > 0.05)。这些观察结果表明,曼氏血吸虫病过程中内源性产生的基因毒性物质可能通过改变Bcl-2蛋白的表达模式来调节凋亡,从而在CRC-Sm发病机制中发挥作用,这与CRC-NSm不同,提示了不同的生物学行为。